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新型β-取代 L-2,3-二氨基丙酸（DAPEG）细胞穿透聚合物及其与核酸相互作用的细胞后果。

Novel Cell Permeable Polymers of -Substituted L-2,3-Diaminopropionic Acid (DAPEGs) and Cellular Consequences of Their Interactions with Nucleic Acids.

机构信息

Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, Poland.

Intercollegiate Faculty of Biotechnology, University of Gdansk Abrahama 58, 80-308 Gdansk, Poland.

出版信息

Int J Mol Sci. 2021 Mar 4;22(5):2571. doi: 10.3390/ijms22052571.

DOI:10.3390/ijms22052571
PMID:33806461
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7961587/
Abstract

The present study aimed to synthesize novel polycationic polymers composed of -substituted L-2,3-diaminopropionic acid residues (DAPEGs) and investigate their cell permeability, cytotoxicity, and DNA-binding ability. The most efficient cell membrane-penetrating compounds (O2Oc-Dap(GO2)-O2Oc-NH, where n = 4, 6, and 8) showed dsDNA binding with a binding constant in the micromolar range (0.3, 3.4, and 0.19 µM, respectively) and were not cytotoxic to HB2 and MDA-MB-231 cells. Selected compounds used in the transfection of a GFP plasmid showed high transfection efficacy and minimal cytotoxicity. Their interaction with plasmid DNA and the increasing length of the main chain of tested compounds strongly influenced the organization and shape of the flower-like nanostructures formed, which were unique for 5/6-FAM-O2Oc-[Dap(GO2)]-O2Oc-NH and typical for large proteins.

摘要

本研究旨在合成新型聚阳离子聚合物，由β取代的 L-2,3-二氨基丙酸残基（DAPEGs）组成，并研究它们的细胞通透性、细胞毒性和 DNA 结合能力。最有效的细胞膜穿透化合物（O2Oc-Dap(GO2)-O2Oc-NH，其中 n = 4、6 和 8）与 dsDNA 结合，结合常数在微摩尔范围内（分别为 0.3、3.4 和 0.19 µM），对 HB2 和 MDA-MB-231 细胞无细胞毒性。用于转染 GFP 质粒的选定化合物表现出高转染效率和最小的细胞毒性。它们与质粒 DNA 的相互作用以及测试化合物主链的长度增加强烈影响形成的花状纳米结构的组织和形状，这对于 5/6-FAM-O2Oc-[Dap(GO2)]-O2Oc-NH 是独特的，对于大型蛋白质是典型的。

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